Acute Toxic and Genotoxic Effects of Aluminum and Manganese Using In Vitro Models
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.1.1. Cell Lines and Treatments
2.1.2. Cytotoxicity Assay
2.1.3. CBMN Cyt Assay
2.1.4. Alkaline Single-Cell Gel Electrophoresis Assay (Comet Assay)
2.2. Ames Test
2.3. Statistical Analysis
3. Results
3.1. Cytotoxicity
3.2. MCN Test
3.3. Comet Assay
3.4. Salmonella Microsome Assay (Ames Test)
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Dhanakumar, S.; Solaraj, G.; Mohanraj, R. Heavy Metal Partitioning in Sediments and Bioaccumulation in Commercial Fish Species of Three Major Reservoirs of River Cauvery Delta Region, India. Ecotoxicol. Environ. Saf. 2015, 113, 145–151. [Google Scholar] [CrossRef]
- Jayaprakash, M.; Kumar, R.S.; Giridharan, L.; Sujitha, S.B.; Sarkar, S.K.; Jonathan, M.P. Bioaccumulation of Metals in Fish Species from Water and Sediments in Macrotidal Ennore Creek, Chennai, SE Coast of India: A Metropolitan City Effect. Ecotoxicol. Environ. Saf. 2015, 120, 243–255. [Google Scholar] [CrossRef]
- Izah, S.C.; Chakrabarty, N.; Srivastav, A.L. A Review on Heavy Metal Concentration in Potable Water Sources in Nigeria: Human Health Effects and Mitigating Measures. Expo. Health 2016, 8, 285–304. [Google Scholar] [CrossRef]
- Van Wendel de Joode, B.; Barbeau, B.; Bouchard, M.F.; Mora, A.M.; Skytt, Å.; Córdoba, L.; Quesada, R.; Lundh, T.; Lindh, C.H.; Mergler, D. Manganese Concentrations in Drinking Water from Villages near Banana Plantations with Aerial Mancozeb Spraying in Costa Rica: Results from the Infants’ Environmental Health Study (ISA). Environ. Poll. 2016, 215, 247–257. [Google Scholar] [CrossRef] [Green Version]
- Lima, P.D.L.; Vasconcellos, M.C.; Montenegro, R.C.; Bahia, M.O.; Costa, E.T.; Antunes, L.M.G.; Burbano, R.R. Genotoxic Effects of Aluminum, Iron and Manganese in Human Cells and Experimental Systems: A Review of the Literature. Hum. Exp. Toxicol. 2011, 30, 1435–1444. [Google Scholar] [CrossRef]
- Krewski, D.; Yokel, R.A.; Nieboer, E.; Borchelt, D.; Cohen, J.; Harry, J.; Kacew, S.; Lindsay, J.; Mahfouz, A.M.; Rondeau, V. Human Health Risk Assessment for Aluminium, Aluminium Oxide, and Aluminium Hydroxide. J. Toxicol. Environ. Health B Crit. Rev. 2007, 10 (Suppl. S1), 1–269. [Google Scholar] [CrossRef]
- Willhite, C.C.; Karyakina, N.A.; Yokel, R.A.; Yenugadhati, N.; Wisniewski, T.M.; Arnold, I.M.F.; Momoli, F.; Krewski, D. Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts. Crit. Rev. Toxicol. 2014, 44 (Suppl. S4), 1–80. [Google Scholar] [CrossRef]
- Ahamad, A.; Raju, N.J.; Madhav, S.; Gossel, W.; Wycisk, P. Impact of Non-Engineered Bhalswa Landfill on Groundwater from Quaternary Alluvium in Yamuna Flood Plain and Potential Human Health Risk, New Delhi, India. Quat. Int. 2019, 507, 352–369. [Google Scholar] [CrossRef]
- Alexandrov, P.N.; Pogue, A.I.; Lukiw, W.J. Synergism in Aluminum and Mercury Neurotoxicity. Integr. Food Nutr. Metab. 2018, 5. [Google Scholar] [CrossRef] [Green Version]
- Verstraeten, S.V.; Aimo, L.; Oteiza, P.I. Aluminium and Lead: Molecular Mechanisms of Brain Toxicity. Arch. Toxicol. 2008, 82, 789–802. [Google Scholar] [CrossRef]
- Bornhorst, J.; Ebert, F.; Hartwig, A.; Michalke, B.; Schwerdtle, T. Manganese Inhibits Poly (ADP-Ribosyl) Ation in Human Cells: A Possible Mechanism behind Manganese-Induced Toxicity? J. Environ. Monit. 2010, 12, 2062–2069. [Google Scholar] [CrossRef] [Green Version]
- Horning, K.J.; Caito, S.W.; Tipps, K.G.; Bowman, A.B.; Aschner, M. Manganese Is Essential for Neuronal Health. Annu. Rev. Nutr. 2015, 35, 71–108. [Google Scholar] [CrossRef] [PubMed]
- Ahn, H.W.; Jeffery, E.H. Effect of Aluminum on Fluoride Uptake by Salmonella Typhimurium TA98; Implications for the Ames Mutagenicity Assay. J. Toxicol. Environ. Health 1994, 41, 357–368. [Google Scholar] [CrossRef] [PubMed]
- Alimba, C.G.; Dhillon, V.; Bakare, A.A.; Fenech, M. Genotoxicity and Cytotoxicity of Chromium, Copper, Manganese and Lead, and Their Mixture in WIL2-NS Human B Lymphoblastoid Cells Is Enhanced by Folate Depletion. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2016, 798–799, 35–47. [Google Scholar] [CrossRef] [PubMed]
- Geyikoglu, F.; Türkez, H.; Bakir, T.O.; Cicek, M. The Genotoxic, Hepatotoxic, Nephrotoxic, Haematotoxic and Histopathological Effects in Rats after Aluminium Chronic Intoxication. Toxicol. Ind. Health 2013, 29, 780–791. [Google Scholar] [CrossRef]
- Paz, L.N.F.; Moura, L.M.; Feio, D.C.A.; Cardoso, M.d.S.G.; Ximenes, W.L.O.; Montenegro, R.C.; Alves, A.P.N.; Burbano, R.R.; Lima, P.D.L. Evaluation of in Vivo and in Vitro Toxicological and Genotoxic Potential of Aluminum Chloride. Chemosphere 2017, 175, 130–137. [Google Scholar] [CrossRef]
- Stephenson, A.P.; Schneider, J.A.; Nelson, B.C.; Atha, D.H.; Jain, A.; Soliman, K.F.A.; Aschner, M.; Mazzio, E.; Renee Reams, R. Manganese-Induced Oxidative DNA Damage in Neuronal SH-SY5Y Cells: Attenuation of Thymine Base Lesions by Glutathione and N-Acetylcysteine. Toxicol. Lett. 2013, 218, 299–307. [Google Scholar] [CrossRef] [Green Version]
- Gonçalves, P.P.; Silva, V.S. Does Neurotransmission Impairment Accompany Aluminium Neurotoxicity? J. Inorg. Biochem. 2007, 101, 1291–1338. [Google Scholar] [CrossRef]
- Peres, T.V.; Schettinger, M.R.C.; Chen, P.; Carvalho, F.; Avila, D.S.; Bowman, A.B.; Aschner, M. Manganese-Induced Neurotoxicity: A Review of Its Behavioral Consequences and Neuroprotective Strategies. BMC Pharmacol. Toxicol. 2016, 17, 57. [Google Scholar] [CrossRef] [Green Version]
- Wang, Z.; Wei, X.; Yang, J.; Suo, J.; Chen, J.; Liu, X.; Zhao, X. Chronic Exposure to Aluminum and Risk of Alzheimer’s Disease: A Meta-Analysis. Neurosci. Lett. 2016, 610, 200–206. [Google Scholar] [CrossRef]
- Preston, R.J.; Au, W.; Bender, M.A.; Brewen, J.G.; Carrano, A.V.; Heddle, J.A.; McFee, A.F.; Wolff, S.; Wassom, J.S. Mammalian In Vivo and In Vitro Cytogenetic Assays: A Report of the U.S. EPA’s Gene-Tox Program. Mutat. Res. 1981, 87, 143–188. [Google Scholar] [CrossRef]
- Erexson, G.L.; Periago, M.V.; Spicer, C.S. Differential Sensitivity of Chinese Hamster V79 and Chinese Hamster Ovary (CHO) Cells in the in Vitro Micronucleus Screening Assay. Mutat. Res. 2001, 495, 75–80. [Google Scholar] [CrossRef]
- OECD. Test No. 487, In Vitro Mammalian Cell Micronucleus Test, OECD Guidelines for the Testing of Chemicals, Section 4; OECD Publishing: Paris, France, 2016. [Google Scholar] [CrossRef]
- Costa, N.D.; Bryant, P.E. Repair of DNA Single-Strand and Double-Strand Breaks in the Chinese Hamster Xrs 5 Mutant Cell Line as Determined by DNA Unwinding. Mutat. Res. 1988, 194, 93–99. [Google Scholar] [CrossRef]
- Darroudi, F.; Natarajan, A.T. Cytological Characterization of Chinese Hamster Ovary X-ray-Sensitive Mutant Cells Xrs 5 and Xrs 6. I. Induction of Chromosomal Aberrations by X-Irradiation and its Modulation with 3-Aminobenzamide and Caffeine. Mutat. Res. 1987, 177, 133–148. [Google Scholar] [CrossRef]
- Kemp, L.M.; Jeggo, P.A. Radiation-Induced Chromosome Damage in X-Ray-Sensitive Mutants (Xrs) of the Chinese Hamster Ovary Cell Line. Mutat. Res. 1986, 166, 255–263. [Google Scholar] [CrossRef]
- Souza, T.A.J.; Franchi, L.P.; Rosa, L.R.; da Veiga, M.A.M.S.; Takahashi, C.S. Cytotoxicity and Genotoxicity of Silver Nanoparticles of Different Sizes in CHO-K1 and CHO-XRS5 Cell Lines. Mutat. Res. Genet. Toxicol. Environ. Mutagen 2016, 795, 70–83. [Google Scholar] [CrossRef]
- Francisco, L.F.V.; do Amaral Crispim, B.; Spósito, J.C.V.; Solórzano, J.C.J.; Maran, N.H.; Kummrow, F.; do Nascimento, V.A.; Montagner, C.C.; De Oliveira, K.M.P.; Barufatti, A. Metals and Emerging Contaminants in Groundwater and Human Health Risk Assessment. Environ. Sci. Pollut. Res. Int. 2019, 26, 24581–24594. [Google Scholar] [CrossRef] [PubMed]
- Brazil National Environment Council (CONAMA). Resolution no 396 of 3 April 2008. 2008. Available online: http://www2.mma.gov.br/port/conama/legiabre.cfm?codlegi=562 (accessed on 20 October 2019).
- Oliveira, R.J.; Ribeiro, L.R.; da Silva, A.F.; Matuo, R.; Mantovani, M.S. Evaluation of Antimutagenic Activity and Mechanisms of Action of Beta-Glucan from Barley, in CHO-K1 and HTC Cell Lines Using the Micronucleus Test. Toxicol. In Vitro 2006, 20, 1225–1233. [Google Scholar] [CrossRef] [PubMed]
- Fenech, M. Cytokinesis-Block Micronucleus Cytome Assay. Nat. Protoc. 2007, 2, 1084–1104. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Singh, N.P.; McCoy, M.T.; Tice, R.R.; Schneider, E.L. A Simple Technique for Quantitation of Low Levels of DNA Damage in Individual Cells. Exp. Cell Res. 1988, 175, 184–191. [Google Scholar] [CrossRef] [Green Version]
- Mortelmans, K.; Zeiger, E. The Ames Salmonella/Microsome Mutagenicity Assay. Mutat. Res. 2000, 455, 29–60. [Google Scholar] [CrossRef]
- OECD. Test. 471: Bacterial Reverse Mutation Test; Organization for Economic Cooperation and Development (OECD): Paris, France, 1997. [Google Scholar]
- R Core Team. R: A Language and Environment for Statistical Computing; R Foundation for Statistical Computing: Vienna, Austria, 2018. [Google Scholar]
- Bernstein, L.; Kaldor, J.; McCann, J.; Pike, M.C. An Empirical Approach to the Statistical Analysis of Mutagenesis Data from the Salmonella Test. Mutat. Res. 1982, 97, 267–281. [Google Scholar] [CrossRef]
- Tang, J.; Zhang, J.; Ren, L.; Zhou, Y.; Gao, J.; Luo, L.; Yang, Y.; Peng, Q.; Huang, H.; Chen, A. Diagnosis of Soil Contamination Using Microbiological Indices: A Review on Heavy Metal Pollution. J. Environ. Manag. 2019, 242, 121–130. [Google Scholar] [CrossRef] [PubMed]
- Petrescu, I.; Sarac, I.; Bonciu, E.; Madosa, E.; Rosculete, C.A.; Butnariu, M. Study Regarding the Cytotoxic Potential of Cadmium and Zinc in Meristematic Tissues of Basil (Ocimum Basilicum L.). Caryologia 2020, 73. [Google Scholar] [CrossRef]
- Bonciu, E.; Firbas, P.; Fontanetti, C.S.; Wusheng, J.; Karaismailoğlu, M.C.; Liu, D.; Menicucci, F.; Pesnya, D.S.; Popescu, A.; Romanovsky, A.V.; et al. An Evaluation for the Standardization of the Allium Cepa Test as Cytotoxicity and Genotoxicity Assay. Caryologia 2018, 71, 191–209. [Google Scholar] [CrossRef] [Green Version]
- Francisco, L.F.V.; Crispim, B.D.A.; Viana, L.F.; Nascimento, H.D.S.; Raposo Junior, J.L.; Grisolia, A.B. Cytotoxicity, Genotoxicity and Mutagenicity of Aluminum, Manganese and Lead in Meristematic Cells of Root Allium Cepa. Orbital Electron. J. Chem. 2018, 10, 60–65. [Google Scholar] [CrossRef]
- Taylor, C.A.; Tuschl, K.; Nicolai, M.M.; Bornhorst, J.; Gubert, P.; Varão, A.M.; Aschner, M.; Smith, D.R.; Mukhopadhyay, S. Maintaining Translational Relevance in Animal Models of Manganese Neurotoxicity. J. Nutr. 2020, 150, 1360–1369. [Google Scholar] [CrossRef]
- Zhao, L.; Xia, Z.; Wang, F. Zebrafish in the Sea of Mineral (Iron, Zinc, and Copper) Metabolism. Front. Pharmacol. 2014, 5. [Google Scholar] [CrossRef] [Green Version]
- Benitez-Trinidad, A.B.; Herrera-Moreno, J.F.; Vázquez-Estrada, G.; Verdín-Betancourt, F.A.; Sordo, M.; Ostrosky-Wegman, P.; Bernal-Hernández, Y.Y.; Medina-Díaz, I.M.; Barrón-Vivanco, B.S.; Robledo-Marenco, M.L.; et al. Cytostatic and Genotoxic Effect of Temephos in Human Lymphocytes and HepG2 Cells. Toxicol. In Vitro 2015, 29, 779–786. [Google Scholar] [CrossRef]
- Demir, E.; Burgucu, D.; Turna, F.; Aksakal, S.; Kaya, B. Determination of TiO2, ZrO2, and Al2O3 Nanoparticles on Genotoxic Responses in Human Peripheral Blood Lymphocytes and Cultured Embyronic Kidney Cells. J. Toxicol. Environ. Health A 2013, 76, 990–1002. [Google Scholar] [CrossRef]
- Gajski, G.; Ladeira, C.; Gerić, M.; Garaj-Vrhovac, V.; Viegas, S. Genotoxicity Assessment of a Selected Cytostatic Drug Mixture in Human Lymphocytes: A Study Based on Concentrations Relevant for Occupational Exposure. Environ. Res. 2018, 161, 26–34. [Google Scholar] [CrossRef] [PubMed]
- Kumar, V.; Bal, A.; Gill, K.D. Impairment of Mitochondrial Energy Metabolism in Different Regions of Rat Brain Following Chronic Exposure to Aluminium. Brain Res. 2008, 1232, 94–103. [Google Scholar] [CrossRef] [PubMed]
- Liaquat, L.; Sadir, S.; Batool, Z.; Tabassum, S.; Shahzad, S.; Afzal, A.; Haider, S. Acute Aluminum Chloride Toxicity Revisited: Study on DNA Damage and Histopathological, Biochemical and Neurochemical Alterations in Rat Brain. Life Sci. 2019, 217, 202–211. [Google Scholar] [CrossRef]
- Xu, F.; Liu, Y.; Zhao, H.; Yu, K.; Song, M.; Zhu, Y.; Li, Y. Aluminum Chloride Caused Liver Dysfunction and Mitochondrial Energy Metabolism Disorder in Rat. J. Inorg. Biochem. 2017, 174, 55–62. [Google Scholar] [CrossRef] [PubMed]
- Kamalov, J.; Carpenter, D.O.; Birman, I. Cytotoxicity of Environmentally Relevant Concentrations of Aluminum in Murine Thymocytes and Lymphocytes. J. Toxicol. 2011, 2011. [Google Scholar] [CrossRef]
- Zhang, L.; Sang, H.; Liu, Y.; Li, J. Manganese Activates Caspase-9-Dependent Apoptosis in Human Bronchial Epithelial Cells. Hum. Exp. Toxicol. 2013, 32, 1155–1163. [Google Scholar] [CrossRef]
- Zhao, F.; Zhang, J.-B.; Cai, T.-J.; Liu, X.-Q.; Liu, M.-C.; Ke, T.; Chen, J.-Y.; Luo, W.-J. Manganese Induces P21 Expression in PC12 Cells at the Transcriptional Level. Neuroscience 2012, 215, 184–195. [Google Scholar] [CrossRef]
- Porte Alcon, S.; Gorojod, R.M.; Kotler, M.L. Regulated Necrosis Orchestrates Microglial Cell Death in Manganese-Induced Toxicity. Neuroscience 2018, 393, 206–225. [Google Scholar] [CrossRef] [PubMed]
- Gonzalez, L.E.; Juknat, A.A.; Venosa, A.J.; Verrengia, N.; Kotler, M.L. Manganese Activates the Mitochondrial Apoptotic Pathway in Rat Astrocytes by Modulating the Expression of Proteins of the Bcl-2 Family. Neurochem. Int. 2008, 53, 408–415. [Google Scholar] [CrossRef]
- Martinez-Finley, E.J.; Gavin, C.E.; Aschner, M.; Gunter, T.E. Manganese Neurotoxicity and the Role of Reactive Oxygen Species. Free Radic. Biol. Med. 2013, 62, 65–75. [Google Scholar] [CrossRef] [Green Version]
- Prabhakaran, K.; Ghosh, D.; Chapman, G.D.; Gunasekar, P.G. Molecular Mechanism of Manganese Exposure-Induced Dopaminergic Toxicity. Brain Res. Bull. 2008, 76, 361–367. [Google Scholar] [CrossRef]
- Tamm, C.; Sabri, F.; Ceccatelli, S. Mitochondrial-Mediated Apoptosis in Neural Stem Cells Exposed to Manganese. Toxicol. Sci. 2008, 101, 310–320. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Celik, H.; Celik, N.; Kocyigit, A.; Dikilitas, M. The Relationship between Plasma Aluminum Content, Lymphocyte DNA Damage, and Oxidative Status in Persons Using Aluminum Containers and Utensils Daily. Clin. Biochem. 2012, 45, 1629–1633. [Google Scholar] [CrossRef] [PubMed]
- Lima, P.D.L.; Vasconcellos, M.C.; Bahia, M.O.; Montenegro, R.C.; Pessoa, C.O.; Costa-Lotufo, L.V.; Moraes, M.O.; Burbano, R.R. Genotoxic and Cytotoxic Effects of Manganese Chloride in Cultured Human Lymphocytes Treated in Different Phases of Cell Cycle. Toxicol. In Vitro 2008, 22, 1032–1037. [Google Scholar] [CrossRef] [PubMed]
- Sarac, N.; Ugur, A.; Karaca, I. Evaluation of Antioxidant and Antimutagenic Activities of Aluminum Chloride. Eur. Oral. Res. 2019, 53, 51–55. [Google Scholar] [CrossRef] [PubMed]
Concentrations (mg/plate) | TA 98 | TA 100 | ||
---|---|---|---|---|
S+ (MR) | S− (MR) | S+ (MR) | S− (MR) | |
NC | 20.33 ± 1.24 | 23.33 ± 1.24 | 122.33 ± 1.88 | 111.33 ± 1.69 |
0.025 | 19.66 ± 0.44 (0.96) | 28.66 ± 3.55 (1.22) | 149.70 ± 8.44 * (1.22) | 149.33 ± 1.11 * (1.34) |
0.05 | 18.66 ± 0.44 (0.93) | 21.00 ± 3.33 (0.90) | 132.70 ± 1.55 * (1.08) | 134.66 ± 3.11 * (1.20) |
0.1 | 24.00 ± 1.30 (1.2) | 27.00 ± 2.00 (1.15) | 163.00 ± 4.00 * (1.33) | 136.50 ± 4.50 * (1.22) |
0.2 | 10.00 ± 0.81 (0.37) | 7.33 ± 0.47 (0.33) | 13.00 ± 0.81 (0.18) | 26.00 ± 4.00 (0.33) |
0.4 | - | 10.33 ± 0.47 (0.46) | 18.00 ± 1.41 (0.25) | 26.50 ± 1.50 (0.34) |
0.6 | - | 11.00 ± 1.41 (0.50) | 17.00 ± 1.63 (0.23) | 15.66 ± 0.94 (0.20) |
0.8 | - | 9.33 ± 0.47 (0.42) | 16.33 ± 1.24 (0.23) | 17.33 ± 1.24 (0.22) |
1.0 | - | 7.66 ± 0.94 (0.34) | 17.00 ± 1.41 (0.23) | 19.00 ± 1.63 (0.24) |
PC | 321.00 ± 11.00 * | 1315.00 ± 8.00 * | 1338.00 ± 11.00 * | 1428.00 ± 6.00 * |
Concentrations (mg/plate) | TA 98 | TA 100 | ||
---|---|---|---|---|
S+ (MR) | S− (MR) | S+ (MR) | S− (MR) | |
NC | 20.33 ± 1.24 | 23.33 ± 1.24 | 122.33 ± 1.88 | 111.33 ± 1.69 |
0.0125 | 25.66 ± 0.88 * (1.26) | 29.66 ± 0.88 * (1.27) | 90.00 ± 6.66 (0.73) | 87.66 ± 1.88 (0.78) |
0.025 | 20.33 ± 0.44 (1.00) | 22.66 ± 1.11 (0.97) | 108.66 ± 2.22 (0.88) | 92.33 ± 2.22 (0.82) |
0.05 | 25.00 ± 1.33 (1.22) | 26.66 ± 3.11 (1.14) | 148.00 ± 5.33 * (1.20) | 108.33 ± 2.22 (0.97) |
0.1 | 10.66 ± 1.24 (0.39) | 8.33 ± 0.94 (0.37) | 18.00 ± 5.00 (0.25) | 12.66 ± 0.47 (0.16) |
0.3 | 14.00 ± 2.16 (0.51) | 9.33 ± 0.47 (0.42) | - | - |
1.0 | 8.66 ± 1.88 (0.32) | 6.50 ± 0.50 (0.29) | - | - |
1.5 | 3.33 ± 0.94 (0.12) | 7.00 ± 0.81 (0.31) | - | - |
PC | 321.00 ± 11.00 * | 1315.00 ± 8.00 * | 1338.00 ± 11.00 * | 1428.00 ± 6.00 * |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Francisco, L.F.V.; Baldivia, D.d.S.; Crispim, B.d.A.; Klafke, S.M.F.F.; Castilho, P.F.d.; Viana, L.F.; Santos, E.L.d.; Oliveira, K.M.P.d.; Barufatti, A. Acute Toxic and Genotoxic Effects of Aluminum and Manganese Using In Vitro Models. Toxics 2021, 9, 153. https://doi.org/10.3390/toxics9070153
Francisco LFV, Baldivia DdS, Crispim BdA, Klafke SMFF, Castilho PFd, Viana LF, Santos ELd, Oliveira KMPd, Barufatti A. Acute Toxic and Genotoxic Effects of Aluminum and Manganese Using In Vitro Models. Toxics. 2021; 9(7):153. https://doi.org/10.3390/toxics9070153
Chicago/Turabian StyleFrancisco, Luiza Flavia Veiga, Debora da Silva Baldivia, Bruno do Amaral Crispim, Syla Maria Farias Ferraz Klafke, Pamella Fukuda de Castilho, Lucilene Finoto Viana, Edson Lucas dos Santos, Kelly Mari Pires de Oliveira, and Alexeia Barufatti. 2021. "Acute Toxic and Genotoxic Effects of Aluminum and Manganese Using In Vitro Models" Toxics 9, no. 7: 153. https://doi.org/10.3390/toxics9070153